. ?Rhabdomyosarcoma cells response to 1,25(OH)2-vitamin D3 inducing MAPK activation and VDR expression?

A. PAULA IRAZOQUI; BOLAND R; BUITRAGO C

Congreso; XXXII Reunión Anual Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2015

Our laboratory has studied for many years the role of the steroid hormone 1,25(OH)2-vitamin D3 [1,25D] in avian and mammalian skeletal muscle cells focused principally on vitamin D receptor (VDR) involvement and signal transduction pathways triggered by this hormone. Recently, we reported VDR and p38 MAPK participation in cell proliferation and differentiation induced by the hormone in the normal murine skeletal muscle cell line C2C12. There is not information about 1,25D actions in rhabdomyosarcoma (RMS) cells. RMS is a soft tissue cancer that affects skeletal muscle predominantly in child and elderly people and includes heterogeneous tumors of mesenchymal derivation which are genetically committed to the myogenic lineage, failing to complete terminal differentiation. In this work, using RD cells, an embryonal rhabdomyosarcoma cell line, we evidenced that hormone promotes rapid effects. Our data indicate that 1 nM of 1,25D activates ERK1/2, p38 MAPK and the p38 MAPK upstream immediately kinases (MKK3/6) rapidly, evidencing that the hormone regulates non genomic transduction pathways in these cells. Moreover, the non receptor tyrosine kinase Src was also activated by 1,25D in RD cells. When ERK1/2 were inhibited with PD98059, Src activation was abolished. MKK3/6 activation was also dependent on ERK1/2 activation. Of relevance, 1,25D increases VDR expression in these cells and this event was dependent on p38 MAPK activation. The results indicate that 1,25D exerts rapid actions in rhabdomyosarcoma cells and open doors to investigate in deep hormone modulation of different signaling pathways in these cancer cells.